In certain instances, human pharmacogenetic disorders cause individuals to react very differently to the same dose of the same drug. The teratogenic, carcinogenic, or toxic effects of certain drugs and other foreign compounds (xenobiotics) also may reflect important genetically mediated differences between individuals. Accordingly, our laboratory has developed experimental model systems for studying drug metabolism in cell culture and among inbred strains of mice. We have found that the induction of more than two dozen drug-metabolizing enzyme activities is regulated by a genetic system called the Ah complex. We have characterized the major regulatory gene product, a cytosolic receptor that binds avidly to certain inducers of P-450; the inducer-receptor complex undergoes a temperature-dependent translocation into the nucleus. Among the structural gene products are multiple forms of P-450--a minimum of 12 induced by way of the Ah receptor. Cloned cDNA associated with mouse liver P1-450 has been isolated and characterized. This entire genetic complex has been a useful probe in demonstrating differences in individual risk for various drug-induced birth defects, other forms of drug toxicity, and environmentally-caused malignancies.